My long-range goal is to assess and improve the capability of diffuse optical methods in detection, diagnosis and therapeutic monitoring of breast cancer. Diffuse optical methods using near-infrared light provide several unique functional parameters (such as total hemoglobin concentration, blood oxygen saturation, blood flow, water and lipid concentration) to enhance tumor sensitivity and specificity. Moreover, deep tissue micro-environment (e.g. vascular leakiness, acidity) can be probed with diffuse fluorescence imaging/spectroscopy. Diffuse optical methods can impact on cancer therapy monitoring and planning at early stages since the metabolic changes due to therapy may precede the anatomical size changes measured by clinical palpation or conventional imaging modalities. I have worked on diffuse optical tomography to detect and characterize breast cancer for -10 years at the University of Pennsylvania. I have acquired excellent education and experience in instrumentation and numerical analysis and also got valuable clinical experience. However, as the research is growing rapidly and expanding more into the clinical regime, more in-depth biomedical training is becoming necessary to translate the diffuse optical technology into the clinic. Therefore, I am proposing to expand my horizons under my mentor, Dr. Arjun Yodh from Physics department and co-mentors, Dr. Mitchell Schnall, Dr. Jerry Glickson from Radiology and Dr. Angela DeMichele from Hematology-Oncology. During this mentored phase (K99), I will take courses to get fundamental training on tumor biology and physiology as well as biostatistics. For K99 research, I will explore the utility of portable diffuse optical device to assess neoadjuvant chemotherapy response of subjects with breast cancer. In the subsequent independent investigator phase (ROO), I will compare fluorescence diffuse optical method using a new optical dye whose concentration corresponds to glucose level with autoradiography/PET on mouse xenograft model of human breast cancer. Once I establish the performance of this dye, I will use it as a surrogate marker for glucose metabolism. I will investigate whether simultaneous monitoring of glucose and oxygen metabolism accessible by all optical methods can enhance the assessment of treatment efficacy. This independent research will pave the ways for molecular imaging in vivo for therapy monitoring and diagnosis when it becomes available for human use.